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Activation of human T lymphocytes by Leishmania lipophosphoglycan
M Kemp1, T G Theander, E Handman
1Department of Infectious Diseases, University Hospital, University of Copenhagen, Denmark.
Insights
Individuals cured of visceral leishmaniasis exhibit T-cell responses to Leishmania lipophosphoglycan (LPG). This suggests T lymphocytes can recognize glycolipid antigens after infection.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Visceral leishmaniasis is a significant global health issue.
- Immune responses to Leishmania parasites are complex.
- Understanding T-cell activation is crucial for vaccine development.
Purpose of the Study:
- To investigate Leishmania antigen-induced lymphocyte activation in individuals cured of visceral leishmaniasis.
- To identify specific Leishmania antigens that elicit T-cell responses.
- To explore the role of glycolipid antigens in human T-cell activation.
Main Methods:
- Isolation of peripheral blood mononuclear cells (PBMC) from cured patients and controls.
- In vitro stimulation of PBMC with Leishmania major lipophosphoglycan (LPG) and other antigens.
- Assessment of lymphocyte proliferation and Interferon-gamma production.
- Flow cytometry analysis to identify activated T-cell subsets (CD2-positive).
Main Results:
- PBMC from cured visceral leishmaniasis patients proliferated and produced Interferon-gamma in response to LPG.
- The proliferative response was primarily mediated by CD2-positive T cells.
- Control PBMC did not respond to LPG but reacted to parasite sonicates.
- The surface glycoprotein GP63 did not activate PBMC from any group.
- LPG preparation showed no detectable protein contamination.
Conclusions:
- Individuals cured of visceral leishmaniasis possess expanded T-cell clones recognizing LPG.
- These findings suggest that human T lymphocytes can respond to glycolipid antigens.
- Leishmania LPG is a potential target for immune recognition in visceral leishmaniasis survivors.
Abstract:
This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon-gamma in vitro in response to lipophosphoglycan (LPG) isolated from Leishmania major. The proliferative response was mainly due to activation of CD2-positive T cells. PBMC from controls did not respond to LPG, but to sonicates prepared from both L. major and L. donovani promastigotes. The surface glycoprotein GP 63 failed to activate PBMC from any of the donors tested. These results show that the individuals cured from visceral leishmaniasis had expanded T-cell clones recognizing LPG, conceivably as a result of Leishmania infection. The LPG preparation was without detectable protein contamination. Thus, the results suggest that human T lymphocytes can respond to glycolipid antigens.